DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
Claims 1, 4, 11-18, 35, 37-40, 42, 43, 50-61, & 63 filed on 12/12/2025 are pending. Claims 5-10, 36, 44-49, & 64-69 are withdrawn from consideration as being drawn to a non-elected invention. Claims 1, 3, 14, 35, 36, 37, 42, 54, 56, & 57 are currently under examination directed to the elected species of SEQ ID NO: 5 in claim 1, of SEQ ID NO: 20 in claim 1, of SEQ ID NO: 84 in claims 3, 42, 54, & 56, of SEQ ID NO: 21 in claim 14, of SEQ ID NO: 19 in claims 35 & 36, of SEQ ID NO: 2 in claim 37, of SEQ ID NO: 3 in claims 54 & 57, and of SEQ ID NO: 18 in claims 54 & 57 (see response dated 07/11/2025). The cancellation of claims 2, 3, 41, 62, & 70-89 without prejudice or disclaimer in the reply filed 12/12/2025 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 103
Claim(s) 1, 4, 11-18, 35, 37-40, 42, 43, 50-61, & 63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Peterson (Peterson et al.; Journal of Clinical Microbiology, Vol. 53, pages 2042-2048, April 2015), in view of Linnen (U.S. Patent No. 7,785,844 B2), Catanzariti (U.S. Patent No. 6,558,901 B1), and Hokynar (Hokynar et al.; Microorganisms, Vol. 7, pages 1-12, July 2019).
Regarding claims 1, 4, 14-18, 54-57, & 63, Peterson teaches the detection of single nucleotide polymorphisms in Neisseria gonorrhoeae strains and isolates in with the porB assay contained a fluorescent probe (second oligonucleotide probe comprising a backbone and a label) to detect the wildtype (WT) allele (label of the second oligonucleotide probe produces a signal if hybridized to a wildtype and does not produce a signal if hybridized to a variant) and a fluorescent internal positive-control probe (first oligonucleotide probe comprising a backbone and a label) that was detected in all isolates (a label that produces a signal if the first oligonucleotide probe hybridizes to wildtype and a label that produces a detectable signal if the first oligonucleotide probe hybridizes to a variant) wherein the relative fluorescence of a probe minus the baseline is detected in the porB assay (the label of the first oligonucleotide probe is the same as the label of the second oligonucleotide probe) (abstract lines 3-10; pg. 2043-2044 paragraph bridging pg. 2043 & pg. 2044 lines 8-19; pg. 2044 column 1 1st full paragraph lines 1-13; Table 2).
Peterson does not teach that the label is attached to the backbone by a non-nucleotide linker and probes in a composition with a promoter-primer.
Linnen teaches hybridization probes and amplification primers for the detection of viral nucleic acids in which the probes that hybridize to target sequences can include a detectable label that is joined to the probe by a non-nucleotide linker and that the detectably labeled probes can comprise one or more modified nucleosides including a 2’-O-methyl substitution (probe(s) comprise one or more 2’-methoxy chemical groups) (column 21 lines 26-30 & 39-47). Linnen also teaches kits (compositions) comprising hybridization probes and amplification primers for the detection of viral nucleic acids in which the primers encompass primers containing an upstream promoter sequence that and a target hybridization site that is from the 3’ end (a downstream target-hybridizing sequence) (column 10 lines 47-62). Linnen also teaches that the labeling of the probe allows for monitoring specific nucleic acid hybridization (column 11 lines 55-64).
Peterson and Linnen are considered to be analogous to the claimed invention because they are all in the same field of detection of nucleic acid sequences with oligonucleotide probes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the a fluorescent probes (first and second oligonucleotide probe comprising a backbone and a label) in Peterson to incorporate probe(s) in a composition with a promoter-primer in which a label that is attached to the backbone by a non-nucleotide linker as taught in Linnen because Linnen teaches that doing so would provide a way to label probes that allows for the monitoring of specific nucleic acid hybridization.
Peterson and Linnen does not teach that the fluorescent internal positive-control probe (first oligonucleotide comprising a backbone and a label) has a sequence of bases attached to the backbone in which the sequence of bases comprising SEQ ID NO: 66 (see claims 1 & 18) or SEQ ID NO: 84 (see claims 3, 54, & 56), that the base sequence of the second oligonucleotide probe is SEQ ID NO: 38 (see claim 17), or that the fluorescent internal positive-control probe (first oligonucleotide comprising a backbone and a label) hybridizes to a wildtype and to a variant C. trachomatis.
Catanzariti teaches internal control oligonucleotides designed for the detection of Chlamydia trachomatis (CT) in which the CT internal control target SEQ ID NO: 11 comprises SEQ ID NO: 66 of the instant application from positions 71 to 89, SEQ ID NO: 84 of the instant application from positions 70 to 90, and SEQ ID NO: 38 of the instant application from positions 31 to 54 (column 8 lines 42-44; column 26 lines 25-43) (column 8 lines 42-44; column 26 lines 25-43). Catanzariti also teaches that the use of an internal control sequence allows for the optimization in detecting specific assays including for detection of CT in a CT assay (column 26 lines 25-32).
Hokynar teaches amplification and sequencing of fragments of the 23S rRNA gene of C. trachomatis in which the sequences were amplified, sequenced, and compared to known C. trachomatis sequences in the NCBI database in which Sanger sequencing detected a single nucleotide position (SNP) at position C1515T (variant C. trachomatis nucleic acid sequence) in the C. trachomatis 23S rRNA gene (pg. 3 3rd full paragraph lines 1-14; pg. 7 1st full paragraph lines 1-11; Figure 5).
Linnen teaches hybridization probes and amplification primers for the detection of viral nucleic acids in which the probes that hybridize to target sequences can include a detectable label that is joined to the probe by a non-nucleotide linker and that this non-nucleotide linker can be in different linker positions and that the use of different linker positions confirms the versatility of this labeling technique (column 21 lines 39-45; column 30 lines 16-50).
Peterson, Linnen, Catanzariti, and Hokynar are considered to be analogous to the claimed invention because they are all in the same field of detection of nucleic acid sequences with oligonucleotide probes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fluorescent internal positive-control probe (first oligonucleotide probe comprising a backbone and a label) and the fluorescent probe (second oligonucleotide probe comprising a backbone and a label) for detecting bacterial species taught by Peterson and Linnen to construct a probe for wildtype and variant C. trachomatis with a first oligonucleotide probe comprising a sequence of bases attached to the backbone, the sequence of bases comprising SEQ ID NO: 66 or SEQ ID NO: 84, and a probe for wildtype C. trachomatis with a second oligonucleotide probe comprising a sequence of bases comprising SEQ ID NO: 38, because Catanzariti teaches an internal control oligonucleotide, SEQ ID NO: 11 (of Catanzariti) which comprises SEQ ID NO: 66, SEQ ID NO: 84, and SEQ ID NO: 38 of the instant application for the detection of Chlamydia trachomatis (CT) while Hokynar teaches the SNP at position C1515T (variant C. trachomatis nucleic acid sequence) and the routine construction of primers and probes and aligning sequences to find conservations and variants within the sequences. Absent secondary considerations, the first oligonucleotide probe with an sequence of bases, comprising SEQ ID NO: 66 or SEQ ID NO: 84 of the instant application, attached to the backbone, these probes are considered obvious in view of the teachings of the prior art.
Further, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have optimized the probe taught by Peterson in view of Linnen, Catanzariti, and Hokynar to incorporate the linker in different positions of the backbone as taught in Linnen because Linnen exemplifies the routine nature of optimizing linker placement and Linnen teaches that doing so provides a versatile labeling technique (see MPEP §2144.05.II).
Regarding claims 11-13, & 58-60, Linnen teaches that the detectable label that is joined to the probe by a non-nucleotide linker in which the detectable label is a chemiluminescent acridinium ester compound and Linnen teaches that the detectably labeled probes comprises one or more modified nucleosides including a 2’-O-methyl substitution (one or more 2’-methoxy chemical groups) (column 21 lines 26-30 & 39-47).
Regarding claims 35, 38, 42, 43 & 50, Peterson teaches the detection of single nucleotide polymorphisms in Neisseria gonorrhoeae strains and isolates in with the ponA assay contained a fluorescent forward probe (first oligonucleotide probe comprising backbone and a label) to detect the wildtype (WT) allele (a label that produces a detectable signal if hybridized to wildtype but does not produce a signal if hybridized to a variant) and a fluorescent reverse probe (second oligonucleotide probe comprising backbone and a label) to detect a SNP (a label that produces a signal hybridizes to a variant) wherein the relative fluorescence of a probe minus the baseline is detected in the ponA assay (the label of the first and second oligonucleotide probe is the same) (abstract lines 3-10; pg. 2043-2044 paragraph bridging pg. 2043 & pg. 2044 lines 8-19; pg. 2044 column 1 1st full paragraph lines 1-13; Table 2).
Peterson does not teach that the label is attached to the backbone by a non-nucleotide linker (see claim 38).
Linnen teaches hybridization probes and amplification primers for the detection of viral nucleic acids in which the probes that hybridize to target sequences can include a detectable label that is joined to the probe by a non-nucleotide linker (column 21 lines 39-45; column 28 lines 25-65; column 30 lines 16-50). Linnen also teaches that the labeling of the probe allows for monitoring specific nucleic acid hybridization (column 11 lines 55-64).
Peterson and Linnen are considered to be analogous to the claimed invention because they are all in the same field of detection of nucleic acid sequences with oligonucleotide probes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fluorescent probes (first and second oligonucleotide probe comprising a backbone and a label) in Peterson to incorporate a label that is attached to the backbone by a non-nucleotide linker as taught in Linnen because Linnen teaches that doing so would provide a way to label probes that allows for the monitoring of specific nucleic acid hybridization.
Peterson and Linnen does not teach that the second oligonucleotide has a sequence of bases attached to the backbone in which the sequence of bases comprising SEQ ID NO: 66 attached at base position 11 and 12 (see claim 41) or the sequence of SEQ ID NO: 84 attached at base position 12 and 13 (see claims 42 & 43), or that the fluorescent forward and fluorescent reverse probe (first oligonucleotide probe and second oligonucleotide probe) hybridizes to a wildtype and to a variant C. trachomatis, respectively.
Catanzariti teaches internal control oligonucleotides designed for the detection of Chlamydia trachomatis (CT) in which the CT internal control target SEQ ID NO: 11 encompasses SEQ ID NO: 66 of the instant application from positions 71 to 89 and SEQ ID NO: 84 of the instant application from positions 70 to 90 (column 8 lines 42-44; column 26 lines 25-43). Catanzariti also teaches that the use of an internal control oligonucleotide allows for the optimization in detecting specific assays including for detection of CT in a CT assay (column 26 lines 25-32).
Hokynar teaches amplification and sequencing of fragments of the 23S rRNA gene of C. trachomatis in which the sequences were amplified, sequenced, and compared to known C. trachomatis sequences in the NCBI database in which Sanger sequencing detected a single nucleotide position (SNP) at position C1515T (variant C. trachomatis nucleic acid sequence) in the C. trachomatis 23S rRNA gene (pg. 3 3rd full paragraph lines 1-14; pg. 7 1st full paragraph lines 1-11; Figure 5).
Linnen teaches hybridization probes and amplification primers for the detection of viral nucleic acids in which the probes that hybridize to target sequences can include a detectable label that is joined to the probe by a non-nucleotide linker and that this non-nucleotide linker can be in different linker positions and that the use of different linker positions confirms the versatility of this labeling technique (column 21 lines 39-45; column 30 lines 16-50).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fluorescent forward probe (first oligonucleotide probe comprising a backbone and a label) and the fluorescent reverse probe (second oligonucleotide probe comprising a backbone and a label) in bacterial species taught by Peterson and Linnen to construct a probe for the detection of wildtype and variant C. trachomatis with a second oligonucleotide probe comprising a sequence of bases attached to the backbone, the sequence of bases comprising SEQ ID NO: 66 or SEQ ID NO: 84, because Catanzariti teaches an internal control oligonucleotide, SEQ ID NO: 11 (of Catanzariti) which encompasses SEQ ID NO: 66 and SEQ ID NO: 84 of the instant application for the detection of Chlamydia trachomatis (CT) while Hokynar teaches the SNP at position C1515T (variant C. trachomatis nucleic acid sequence) and the routine construction of primers and probes and aligning sequences to find conservations and variants within the sequences. Absent secondary considerations, the second oligonucleotide probe with an sequence of bases, comprising SEQ ID NO: 66 or SEQ ID NO: 84 of the instant application, attached to the backbone, these probes are considered obvious in view of the teachings of the prior art.
Further, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have optimized the probe taught by Peterson in view of Linnen, Catanzariti, and Hokynar to incorporate the linker in different positions of the backbone as taught in Linnen because Linnen exemplifies the routine nature of optimizing linker placement and Linnen teaches that doing so provides a versatile labeling technique (see MPEP §2144.05.II).
Regarding claim 37, Linnen teaches kits (compositions) comprising hybridization probes and amplification primers for the detection of viral nucleic acids in which the primers encompass primers containing an upstream promoter sequence that and a target hybridization site that is from the 3’ end (a downstream target-hybridizing sequence) (column 10 lines 47-62).
Regarding claims 39, 40, & 51-53, Peterson teaches a fluorescent forward probe (first oligonucleotide probe comprising DNA backbone and a label) to detect the wildtype (WT) allele and a fluorescent reverse probe (second oligonucleotide probe comprising DNA backbone and a label) to detect a SNP (a label that produces a signal hybridizes to a variant) wherein the relative fluorescence of a probe minus the baseline is detected in the ponA assay (the label of the first and second oligonucleotide probe is the same) (abstract lines 3-10; pg. 2043-2044 paragraph bridging pg. 2043 & pg. 2044 lines 8-19; pg. 2044 column 1 1st full paragraph lines 1-13; Table 2).
Linnen teaches that the detectable label that is joined to the probe by a non-nucleotide linker in which the detectable label is a chemiluminescent acridinium ester compound and Linnen teaches that the detectably labeled probes can comprise one or more modified nucleosides including a 2’-O-methyl substitution (the first and/or second oligonucleotide probe can comprise at least one 2’-methoxy chemical groups) (column 21 lines 26-30 & 39-47).
Regarding claim 61, Linnen teaches kits (compositions) comprising hybridization probes and amplification primers for the detection of viral nucleic acids can further comprise a reverse transcriptase and an RNA polymerase (column 10 lines 58-64).
Response to Arguments
The response traverses the rejection. The response asserts that the present claims are amended to recite particular base sequences and positions of a non-nucleotide linker that yielded probes having particularly desirable properties, where those structures and properties could not have been predicted or derived from the cited prior art and therefore none of the cited references, alone or in combination, teaches or suggests a probe reagent or kit for detecting wildtype and variant C. trachomatis target nucleic acids as presently recited. Specifically, the response asserts that both the sequence and presence and positioning of the non-nucleotide linker dramatically influenced probe signaling. Further, the response asserts that the specification of the instant application in Example 2 differ in sequence at a single base (position 7) but share a common non-nucleotide linker attachment site (between bases 9 and 10) and that these two probes differed with respect to their abilities to detect the FIncC1515T C. trachomatis variant sequence and therefore a single base difference clearly affected signaling properties of the probe. Further, the response asserts that the specification of the instant application in Example 3 present structures of SEQ ID NO: 73 and SEQ ID NO: 77, which differed by the positioning of non-nucleotide linkers within base sequences but were otherwise identical and results demonstrated that SEQ ID NO: 73 advantageously gave lower signals with non- C. trachomatis species targets. Further, the response asserts that the claimed probes have particularly desirable properties that could not have been predicted or derived from the cited prior art and specifically that the presently claimed probes produced detectable signals for wildtype and variant C. trachomatis target sequences and that Peterson and Linnen do not teach or suggest the particular probes having base sequences and positions of a non-nucleotide linker recited in the present claims, let alone teach one of ordinary skill how to obtain the unexpected results and advantageous properties discussed above. Further, the response asserts that Catanzariti does not remedy the deficiencies of Peterson and Linnen as Catanzariti is silent regarding the particular probe sequences and the topic of non-nucleotide linkers and that SEQ ID NO: 11 of Catanzariti would not have suggested any of the presently claimed sequences to one skilled in the art for the reasons described above and in view of the immense number of combinatorial possibilities that one skilled in the art would need to explore to arrive at the claimed probes. Finally, the response asserts that Hokynar does not remedy the deficiencies of Peterson, Linnen, and Catanzariti as Hokynar does not disclose or suggest a oligonucleotide probe having the unexpected results described above. These arguments have been thoroughly reviewed but were not found persuasive. First, it is noted that the findings of unexpected results must be commensurate in scope with the claimed inventions (see MPEP §716.02(d)). The claims recite limitations of comprising a first oligonucleotide probe having a sequence of bases comprising SEQ ID NO: 66 and further wherein the sequence of bases attached to the backbone of the first oligonucleotide probe is SEQ ID NO: 84, SEQ ID NO: 85, etc. which is broader, and therefore not commensurate in scope, with the results discussed in the response. The response asserts that both the base sequence, and therefore the particular oligonucleotide composition, AND the linker position within the probe contribute to the specificity of signal generation, however the claims as currently amended recite comprising “open” language, thereby allowing for sequences on either side of the recited SEQ ID Nos. Accordingly, the scope of the claims does not appear to be commensurate in scope with the unexpected results attributed to particular sequences and their linker positions discussed in the response and taught in the specification. If a “single base difference clearly affected signaling properties of the probe” (see response filed 12/12/2025 at pg. 15), then the arguments in the response appear to be contradictory to the broader scope encompassed by the claims.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1, 4, 11-18, 35, 37-40, 42, 43, 50-61, & 63 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682